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Title: Microsatellite instability and immune checkpoint inhibitors: toward precision medicine against gastrointestinal and hepatobiliary cancers
Authors: Eso, Yuji  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0003-4426-1491 (unconfirmed)
Shimizu, Takahiro  kyouindb  KAKEN_id
Takeda, Haruhiko
Takai, Atsushi  kyouindb  KAKEN_id
Marusawa, Hiroyuki
Author's alias: 惠莊, 裕嗣
清水, 孝洋
髙井, 淳
丸澤, 宏之
Keywords: Gastric cancer
Hepatocellular carcinoma
Immune checkpoint inhibitor
Microsatellite instability
Pancreatic cancer
Issue Date: Jan-2020
Publisher: Springer Nature
Journal title: Journal of Gastroenterology
Volume: 55
Start page: 15
End page: 26
Abstract: Recent innovations in the next-generation sequencing technologies have unveiled that the accumulation of genetic alterations results in the transformation of normal cells into cancer cells. Accurate and timely repair of DNA is, therefore, essential for maintaining genetic stability. Among various DNA repair pathways, the mismatch repair (MMR) pathway plays a pivotal role. MMR deficiency leads to a molecular feature of microsatellite instability (MSI) and predisposes to cancer. Recent studies revealed that MSI-high (MSI-H) or mismatch repair-deficient (dMMR) tumors, regardless of their primary site, have a promising response to immune checkpoint inhibitors (ICIs), leading to the approval of the anti-programmed cell death protein 1 monoclonal antibody pembrolizumab for the treatment of advanced or recurrent MSI-H/dMMR solid tumors that continue to progress after conventional chemotherapies. This new indication marks a paradigm shift in the therapeutic strategy of cancers; however, when considering the optimum indication for ICIs and their safe and effective usage, it is important for clinicians to understand the genetic and immunologic features of each tumor. In this review, we describe the molecular basis of the MMR pathway, diagnostics of MSI status, and the clinical importance of MSI status and the tumor mutation burden in developing therapeutic strategies against gastrointestinal and hepatobiliary malignancies.
Rights: ©The Author(s) 2019
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
URI: http://hdl.handle.net/2433/245658
DOI(Published Version): 10.1007/s00535-019-01620-7
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